Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibition of the Calcineurin Pathway by Two Flavonoids Isolated from Miliusa sinensis Finet & Gagnep.

  • Lee, Won Jeong (Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology) ;
  • Moon, Jae Sun (Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Young Tae (Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology) ;
  • Bach, Tran The (Vietnam Academy of Science and Technology (VAST)) ;
  • Hai, Do Van (Vietnam Academy of Science and Technology (VAST)) ;
  • Kim, Sung Uk (Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2016.05.19
  • Accepted : 2016.06.20
  • Published : 2016.10.28
Download PDF
⟨ Previous Next ⟩

Abstract

In order to discover plant-derived signaling pathway inhibitors with antifungal properties, a two-component screening system utilizing the calcineurin and Hog1 mitogen-activated protein kinase pathways responsible for the virulence networks of Cryptococcus neoformans was employed, owing to the counter-regulatory actions of these pathways. Of the 1,000 plant extracts tested, two bioactive compounds from Miliusa sinensis were found to act specifically on the calcineurin pathway of C. neoformans. These compounds, identified as pashanone and 5-hydroxy-6,7-dimethoxyflavanone, exhibited potent antifungal activities against various human pathogenic fungi with minimum inhibitory concentration values ranging from 4.0 to >128 μg/ml.

Keywords

References

  1. Bahn YS. 2008. Master and commander in fungal pathogens: the two-component system and the Hog signaling pathway. Eukaryot. Cell 7: 2017-2036. https://doi.org/10.1128/EC.00323-08
  2. Bahn YS, Kojima K, Cox GM, Heitman J. 2005. Specialization of the Hog pathway and its impact on differentiation and virulence of Cryptococcus neoformans. Mol. Biol. Cell 16: 2285-2300. https://doi.org/10.1091/mbc.E04-11-0987
  3. Bahn YS, Kojima K, Cox GM, Heitman J. 2006. A unique fungal two-component system regulates stress responses, drug sensitivity, sexual development, and virulence of Cryptococcus neoformans. Mol. Biol. Cell 17: 3122-3135. https://doi.org/10.1091/mbc.E06-02-0113
  4. Clinical and Laboratory Standards Institute. 2008. Reference Methods for Broth Dilution Antifungal Susceptibility Testing of Yeasts, pp. 1-20, 3rd Ed. CLSI Document M27-A3. Clinical and Laboratory Standards Institute, Pennsylvania.
  5. Cruz MC, Fox DS, Heitman J. 2001. Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans. EMBO J. 20: 1020-1032. https://doi.org/10.1093/emboj/20.5.1020
  6. Cyert MS. 2003. Calcineurin signaling in Saccharomyces cerevisiae: how yeast go crazy in response to stress. Biochem. Biophys. Res. Commun. 311: 1143-1150. https://doi.org/10.1016/S0006-291X(03)01552-3
  7. Fujita M, Suqiura R, Lu Y, Xu L, Xia Y, Shuntoh H, Kuno T. 2002. Genetic interaction between calcineurin and type 2 myosin and their involvement in the regulation of cytokinesis and chloride ion homeostasis in fission yeast. Genetics 161: 971-981.
  8. Hull CM, Heitman J. 2002. Genetics of Cryptococcus neoformans. Annu. Rev. Genet. 36: 557-615. https://doi.org/10.1146/annurev.genet.36.052402.152652
  9. Huong DT, Luong DV, Thao TTP, Sung TV. 2005. A new flavone and cytotoxic activity of flavonoid constituents isolated from Miliusa balansae (Annonaceae). Pharmazie 60: 627-629.
  10. Ichino K, Tanaka H, Ito K. 1988. Synthesis of helilandin B, pashanone, and their isomers. J. Nat. Prod. 51: 906-914. https://doi.org/10.1021/np50059a015
  11. Idnurm A, Bahn YS, Nielsen K, Lin X, Fraser JA, Heitman J. 2005. Deciphering the model pathogenic fungus Cryptococcus neoformans. Nat. Rev. Microbiol. 3: 753-764. https://doi.org/10.1038/nrmicro1245
  12. Jumana S, Hasan CM, Rashid MA. 2000. Alkaloids from the stem of Miliusa velutina. Biochem. Syst. Ecol. 28: 483-485. https://doi.org/10.1016/S0305-1978(99)00083-6
  13. Kamperdick C, Van NH, Sung TV. 2002. Constituents from Miliusa balansae (Annonaceae). Phytochemistry 61: 991-994. https://doi.org/10.1016/S0031-9422(02)00374-6
  14. Klee CB, Crouch TH, Krinks MH. 1979. Calcineurin: a calcium- and calmodulin-binding protein of the nervous system. Proc. Natl. Acad. Sci. USA 76: 6270-6273. https://doi.org/10.1073/pnas.76.12.6270
  15. Kojima K, Bahn YS, Heitman J. 2006. Calcineurin, Mpk1 and Hog1 MAPK pathways independently control fludioxonil antifungal sensitivity in Cryptococcus neoformans. Microbiology 152: 591-604. https://doi.org/10.1099/mic.0.28571-0
  16. Kozubowski L, Lee SC, Heitman J. 2009. Signalling pathways in the pathogenesis of Cryptococcus. Cell. Microbiol. 11: 370-380. https://doi.org/10.1111/j.1462-5822.2008.01273.x
  17. Lee WJ, Moon JS, Kim SI, Kim YT, Nash O, Bahn YS, Kim SU. 2014. Inhibition of the calcineurin pathway by two tannins, chebulagic acid and chebulanin, isolated from Harrisonia abyssinica Oliv. J. Microbiol. Biotechnol. 24: 1377-1381. https://doi.org/10.4014/jmb.1405.05030
  18. Mendoza I, Quintero FJ, Bressan RA, Hasegawa PM, Pardo JM. 1996. Activated calcineurin confers high tolerance to ion stress and alters the budding patterns and cell morphology of yeast cells. J. Biol. Chem. 271: 23061-23067. https://doi.org/10.1074/jbc.271.27.16344
  19. Mitchell TG, Perfect JR. 1995. Cryptococcosis in the era of AIDS - 100 years after the discovery of Cryptococcus neoformans. Clin. Microbiol. Rev. 8: 515-548.
  20. Poor F, Parent SA, Morin N, Dahl AM, Ramadan N, Chrebet G, et al. 1992. Calcineurin mediates inhibition by FK506 and cyclosporin of recovery from α-factor arrest in yeast. Nature 360: 682-684. https://doi.org/10.1038/360682a0
  21. Sawasdee K, Chaowasku T, Likhitwitayawuid L. 2010. New neolignan and phenylpropanoid glycoside from twigs of Miliusa mollis. Molecules 15: 639-648. https://doi.org/10.3390/molecules15020639
  22. Singh N, Husain S. 2000. Infections of the central nervous system in transplant recipients. Transpl. Infect. Dis. 2: 101-111. https://doi.org/10.1034/j.1399-3062.2000.020302.x
  23. Speed B, Dunt D. 1995. Clinical and host differences between infections with the two varieties of Cryptococcus neoformans. Clin. Infect. Dis. 21: 28-36. https://doi.org/10.1093/clinids/21.1.28
  24. Steinbach WJ, Reedy JL, Cramer Jr RA, Perfect JR, Heitman J. 2007. Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nat. Rev. Microbiol. 5: 418-430. https://doi.org/10.1038/nrmicro1680
  25. Stephen C, Lester S, Black W, Fyfe M, Raverty S. 2002. Multispecies outbreak of cryptococcosis on southern Vancouver Island, British Columbia. Can. Vet. J. 43: 792-794.
  26. Thuy TTT, Quan TD, Ahn NTH, Sung TV. 2011. A new hydrochalcone from Miliusa sinensis. Nat. Prod. Res. 25: 1361-1365. https://doi.org/10.1080/14786419.2011.569505
  27. Wu R, Ye Q, Chen NY, Zhang GL. 2001. A new norditerpene from Miliusa balansae Finet et Gagnep. Chin. Chem. Lett. 12: 247-248.
  28. Zhang HJ, Ma C, Hung NV, Cuong NM, Tan GT, Santarsiero BD, et al. 2006. Miliusanes, a class of cytotoxic agents from Miliusa sinensis. J. Med. Chem. 49: 693-708. https://doi.org/10.1021/jm0509492

Cited by

  1. Genus Miliusa: A Review of Phytochemistry and Pharmacology vol.2019, pp.None, 2019, https://doi.org/10.1155/2019/8314693